The overall objective of the proposed research is to investigate the developmental regulators of drug metabolism and action in experimental animals and humans. These studies will include measurement of the relative capabilities of hepatic and extrahepatic tissues to metabolize multiple classical drug substrates by oxidative and conjugation pathways during pre- and postnatal development. This system will be manipulated by endogenous (hormones and genetic factors) and exogenous (nutrition, disease, chemical and drug exposure) factors to modify the normal developmental pattern of mixed function oxidation and conjugation. In addition, we plan to identify the role of the neuroendocrine (hypothalamus-hypophyseal) axis in the irreversible differentiation and development of drug metabolism and action (drug-receptor binding) in brain. The genetic predisposition as well as prenatal environmental exposure may play an important role in modulating pharmacokinetic parameters, toxicity and teratogenic action of drugs and other foreign compounds. The data generated from these basic investigations will contribute to our understanding of the biochemical mechanisms regulating drug metabolism and action and help in the development of rational, safe and effective drug therapy for sick infants, children and pregnant women.